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This Week in Science

Conformational Selection in Ubiquitin

CREDIT: GUNNAR SHROEDER

Protein dynamics are important to function, but it has been difficult to study dynamics over the relevant time scale—nanoseconds to microseconds. Now Lange et al. (p. 1471; see the Perspective by Boehr and Wright) combine extensive NMR data with molecular dynamics approaches to study molecular fluctuations of the protein ubiquitin in this time frame. Unbound ubiquitin displays collective motions that allow it to sample all configurations found in bound ubiquitin in 46 known crystal structures, in which, for the most part, the bound ubiquitin is in complexes with other proteins. Molecular recognition by ubiquitin can thus be explained by conformational selection rather than by induced fit.

An Internal Probe

Molecular structures are largely determined from the patterns that result when x-ray or electron beams scatter off the molecules placed in their path. Meckel et al. (p. 1478) show that structural information can also be obtained by tracking the momentum of an electron ejected from the molecule itself by a strong laser field. Specifically, electron and ion trajectories were mapped after multiphoton ionization of prealigned gas-phase N2 and O2 by ultrashort laser pulses. The low momentum electrons reveal the geometry of the highest occupied molecular orbital from which they emerged, whereas the high momentum electrons ricochet back to the parent ion and diffract, providing information on the nuclear positions.

Considering Molecular Wires at Length

The resistance of ordinary metallic wires increases linearly as they get longer, but when small molecules are used as wires, the mechanisms that govern electron transport can change as the molecule gets longer and lead to more dramatic changes in conductivity. Experimental studies of this effect can be challenging because the formation of the molecular junction (how it attaches to its metal electrode and how the molecular layer orders) could change as the wires get longer. Choi et al. (p. 1482) avoided this complication by synthesizing conjugated molecules on a gold substrate through reactions that increased the length in a stepwise fashion from 1 to 7 nanometers. A metal-coated atomic force microscope tip was used to measure conductivity, and the expected change from a tunneling to a hopping transport mechanism was observed, as well as a drop of conductivity when nonconjugated units were introduced into the molecule's backbone.

Different Partners Are Stronger

CREDIT: SUBEDI ET AL.

The nuclei of atoms contain protons and neutrons, which do not behave independently within the nucleus: Some of the particles tend to pair up, in essence creating locally within the nucleus a higher effective density. Subedi et al. (p. 1476, published online 29 May) explored the nature of these nucleon pairs by beaming high-energy electrons into a carbon-12 foil to displace protons and neutrons. By examining the type and momentum of the displaced nucleons, the authors determined that most of the pairs were mixed neutron-proton pairs. This finding may have implications for understanding neutron stars, where the particle density is particularly high.

Ozone's Influence

In recent decades, the westerly winds of the southern hemispheric jet stream have accelerated on the poleward side of the jet; this acceleration has been attributed to a combination of effects from increasing greenhouse gas concentrations and decreasing amounts of stratospheric ozone, and this strengthening has been predicted to continue. Son et al. (p. 1486) find differently. A recent set of models, which include fully interactive stratospheric chemistry, project that the summer tropospheric westerly winds in the Southern Hemisphere will decrease on the poleward side of the jet, owing to the gradual diminution of the ozone hole through the year 2050. This would have important consequences for climate in the Southern Hemisphere, and highlights the importance of stratospheric ozone recovery as an agent of climate change.

Acid Tests

A somewhat neglected but extremely important consequence of the ongoing anthropogenic rise in the concentration of atmospheric carbon dioxide is that the ocean is becoming more acidic as it absorbs more of the gas. This acidification is making seawater more corrosive toward calcium carbonate, the material used by many marine organisms to make their exoskeletons. Feely et al. (p. 1490, published online 22 May) report results from 13 hydrographic transects from southern Canada to northern Mexico. Potentially corrosive seawater upwelled onto large portions of the continental shelf in 2007. Such seasonal upwelling of such waters onto the shelf is a natural phenomenon, but the ocean uptake of anthropogenic CO2 has exposed increasing portions of the shelf to potentially damaging effects.

Fat Controller

The synthesis of lipids in the liver depends on transcriptional pathways under the influence of carbohydrate intake. Lee et al. (p. 1492; see the Perspective by Horton) provide evidence for a rather unexpected addition to the list of transcription factors involved in lipid metabolism, XBP1. XBP1 is already known to regulate the unfolded protein response (UPR) in the endoplasmic reticulum, influencing the secretory capacity of a variety of cell types. Mice lacking XBP1 expression in the liver after birth showed reduced levels of cholesterol and triglycerides as a result of attenuated lipid synthesis in the liver. In wild-type mice, XBP1 was induced by the feeding of carbohydrates and corresponded with the expression of several other genes associated with fatty-acid synthesis. It remains unclear exactly how XBP1 helps regulate the complex lipogenic transcriptional network in response to carbohydrate intake.

Location Matters

CREDIT: SANCAK ET AL.

The signaling pathway through which cells modulate protein synthesis and cell growth in response to amino acids has been tricky to unravel. Sancak et al. (p. 1496, published online 22 May) add a key piece to the puzzle with experiments that reveal a role for a group of small guanosine triphosphatases known as Rag proteins (RagA, -B, -C, and -D). RagC associates with the mTORC1 protein kinase complex, a key regulator of cell growth. This interaction of Rag proteins with mTORC1 appears to be necessary and sufficient to convey nutrient availability signals when cells are exposed to amino acids. The physical interaction of Rag proteins with mTORC1 appears not to regulate activity of mTOR, but to influence its localization within the endomembrane system of the cell.

The Wood and the Trees

Predicting the effects of habitat destruction on individual species in real ecosystems is key to conservation planning. The Spanish Forest Inventory, which consists of >98,000 plots across the forested parts of mainland Spain, represents the largest tree data set available for which the presence and absence of different tree species have been quantified. Using this data set, Montoya et al. (p. 1502) analyzed the relationship between habitat loss and species persistence for 34 Iberian tree species at large spatial scales. Differences in responses to deforestation (in terms of species persistence at inventoried sites) were driven strongly by the dispersal mechanism: tree species with animal-dispersed seeds were more resistant to deforestation than those with wind-dispersed seeds and, in six cases, individual tree species actually responded positively to locally reduced tree cover. This relationship might not persist, however, if populations of dispersal vectors in turn begin to suffer from the effects of deforestation themselves.

Damage Detection

A break in both strands of the DNA double helix is potentially very dangerous for organisms because the free ends can recombine inappropriately with other parts of the genome and cause substantial damage. Eukaryotic cells sense and attempt to repair such breaks very rapidly, through the recruitment of DNA repair proteins to the sites of damage, forming nuclear repair foci. Soutoglou and Misteli (p. 1507, published online 15 May) have tethered various repair factors individually to unbroken DNA in human tissue culture cells and find that, surprisingly, even in the absence of DNA damage, repair foci form at the tether site. The DNA damage response may thus involve amplification of the damage-signaling cascade, and the damage-sensing proteins may detect alterations in the higher-order structure of chromatin around the break.

Training, Transfer, and the Striatum

Training causes task-specific performance enhancement and altered patterns of brain activity. Training can also improve performance of untrained related or transfer tasks. Dahlin et al. (p. 1510) trained human subjects on a letter memory task for several weeks. Compared to controls, these subjects showed significant improvements over time, and this training also improved an untrained, but related task. No transferred improvement was observed in an unrelated task. Simultaneous brain-imaging scans revealed that transfer after updating training was mediated by the striatum, in line with predictions from computational modeling that the striatum plays a key role in updating working memory.

Mapping the Yeast Protein Interaction Network

To move beyond genes to an understanding of networks, it is necessary to track protein-protein interactions in vivo. Tarassov et al. (p. 1465, published online 8 May) have used protein-fragment complementation assays, which are based on reassembly of two domains of the enzyme dihydrofolate reductase that have been fused to the proteins of interest, to look at the protein interaction network, the interactome, in yeast. In addition to confirming known interactions within complexes, insights were obtained into the network underlying autophagy, a conserved process by which cells digest their own constituents in response to starvation, and a network underlying cellular polarization during the cell cycle.

The Dark Side

During development and differentiation, some filamentous fungi produce antibiotics and toxins as secondary metabolites. Bayram et al. (p. 1504; see the Perspective by Fischer) report that the trimeric VelB/VeA/LaeA complex, termed the velvet complex, coordinates control of light-responsive fungal development and secondary metabolism. In the dark, the VeA bridges LaeA, the nuclear regulator of secondary metabolism, to VelB, a protein necessary for sexual development. Light results in decreased VeA in the nucleus, thus disrupting the trimeric complex with a subsequent reduction in the production of secondary metabolites.

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